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Targeting xenobiotic receptors PXR and CAR in human diseases

Monimoy Banerjee1, Delira Robbins1, Taosheng Chen1

  • 1Department of Chemical Biology and Therapeutics, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.

Drug Discovery Today
|December 3, 2014
PubMed

Insights

Pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are key targets for drug discovery in diseases like cancer and diabetes. This review explores strategies for developing small molecules to target these nuclear receptors for therapeutic benefits.

Area of Science:

  • Pharmacology and Molecular Biology
  • Nuclear Receptor Signaling
  • Drug Discovery

Background:

  • Nuclear receptors, including pregnane X receptor (PXR) and constitutive androstane receptor (CAR), play critical roles in xenobiotic metabolism and disposition.
  • Dysregulation of PXR and CAR pathways is implicated in various human diseases, such as cancer, diabetes, inflammatory conditions, metabolic disorders, and liver diseases.
  • These receptors represent promising therapeutic targets for a range of human pathologies.

Purpose of the Study:

  • To review and propose strategies for targeting PXR and CAR pathways for therapeutic applications.
  • To explore the potential of small molecules in modulating PXR- and/or CAR-mediated disease-related pathways.
  • To consider the structural differences between PXR and CAR when designing targeted therapies.

Main Methods:

  • Literature review of PXR and CAR functions in disease.
  • Analysis of existing and potential small molecule modulators.
  • Comparative analysis of PXR and CAR structures to inform targeting strategies.

Main Results:

  • PXR and CAR are validated targets for modulating drug metabolism and treating diseases.
  • Individual or simultaneous targeting of PXR and CAR offers therapeutic potential.
  • Structural insights can guide the development of selective or dual-acting agents.

Conclusions:

  • Targeting PXR and CAR holds significant promise for developing novel therapeutics for diverse human diseases.
  • Further research into small molecule development is warranted to exploit these nuclear receptors.
  • Understanding structural nuances is key to optimizing therapeutic strategies for PXR and CAR.

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